A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass.
A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass.
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DOI：
10.2337/dc12-2255
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发表时间：
2013-07
期刊：
影响因子：
16.2
通讯作者：
Argyropoulos G
中科院分区：
文献类型：
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作者：
Gerhard GS;Styer AM;Wood GC;Roesch SL;Petrick AT;Gabrielsen J;Strodel WE;Still CD;Argyropoulos G
Roux-en-Y胃旁路术（RYGB）可以缓解2型糖尿病，但其机制尚不完全清楚。在小鼠中，成纤维细胞生长因子（FGF）15（人类中的FGF 19）调节肝胆汁酸（BA）的产生，也可以解决糖尿病。在这项研究中，我们测试了FGF 19-BA通路在RYGB手术后人类糖尿病缓解中发挥作用的假设。使用不同体重的糖尿病和非糖尿病个体的队列。此外，还研究了无糖尿病的RYGB患者（无糖尿病）、术后至少12个月缓解的RYGB糖尿病患者（糖尿病-R）和术后未缓解的RYGB糖尿病患者（糖尿病-NoR）。使用术前和术后血清样本和术中肝活检比较这些患者组的循环FGF 19和BA水平、肝糖原含量和调节FGF 19-BA途径的基因表达水平。术前，与非糖尿病患者相比，糖尿病患者的FGF 19水平较低，BA水平较高，与体重无关。在接受RYGB的糖尿病患者中，较低的FGF 19水平与调节BA产生的胆固醇7 α-羟化酶1（CYP 7A 1）基因的肝脏表达增加显著相关。然而，在RYGB手术后，与非糖尿病和糖尿病-NoR患者相比，糖尿病-R患者的FGF 19和BA水平（特别是胆酸和脱氧胆酸）表现出更大的增加。综上所述，基线和术后数据表明FGF 19-CYP 7A 1-BA途径在RYGB手术后2型糖尿病的病因学和缓解中起作用。
Roux-en-Y gastric bypass (RYGB) in humans can remit type 2 diabetes, but the operative mechanism is not completely understood. In mice, fibroblast growth factor (FGF) 15 (FGF19 in humans) regulates hepatic bile acid (BA) production and can also resolve diabetes. In this study, we tested the hypothesis that the FGF19–BA pathway plays a role in the remission of human diabetes after RYGB surgery. Cohorts of diabetic and nondiabetic individuals of various body weights were used. In addition, RYGB patients without diabetes (No-Diabetes), RYGB patients with diabetes who experienced remission for at least 12 months after surgery (Diabetes-R), and RYGB patients with diabetes who did not go into remission after surgery (Diabetes-NoR) were studied. Circulating FGF19 and BA levels, hepatic glycogen content, and expression levels of genes regulating the FGF19–BA pathway were compared among these groups of patients using pre- and postoperative serum samples and intraoperative liver biopsies. Preoperatively, patients with diabetes had lower FGF19 and higher BA levels than nondiabetic patients, irrespective of body weight. In diabetic patients undergoing RYGB, lower FGF19 levels were significantly correlated with increased hepatic expression of the cholesterol 7alpha-hydroxylase 1 (CYP7A1) gene, which modulates BA production. Following RYGB surgery, however, FGF19 and BA levels (particularly cholic and deoxycholic acids) exhibited larger increases in Diabetic-R patients compared with nondiabetic and Diabetic-NoR patients. Taken together, the baseline and postoperative data implicate the FGF19–CYP7A1–BA pathway in the etiology and remission of type 2 diabetes following RYGB surgery.
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影响因子：
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作者：
Lillvis JH;Erdman R;Schworer CM;Golden A;Derr K;Gatalica Z;Cox LA;Shen J;Vander Heide RS;Lenk GM;Hlavaty L;Li L;Elmore JR;Franklin DP;Gray JL;Garvin RP;Carey DJ;Lancaster WD;Tromp G;Kuivaniemi H
通讯作者：
Kuivaniemi H
DOI：
10.1038/oby.2009.102
发表时间：
2009-09
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Patti ME;Houten SM;Bianco AC;Bernier R;Larsen PR;Holst JJ;Badman MK;Maratos-Flier E;Mun EC;Pihlajamaki J;Auwerx J;Goldfine AB
通讯作者：
Goldfine AB
影响因子：
3.3
作者：
Gill, Richdeep S.;Sharma, Arya M.;Karmali, Shahzeer
通讯作者：
Karmali, Shahzeer
影响因子：
13.5
作者：
Han, SL;Studer, E;Dent, P
通讯作者：
Dent, P
影响因子：
5.3
作者：
Goetz, Regina;Beenken, Andrew;Mohammadi, Moosa
通讯作者：
Mohammadi, Moosa